Overview

The goal of this randomized controlled trial is to compare letrozole alone versus letrozole plus levothyroxine for ovulation induction in infertile women with both PCOS and subclinical hypothyroidism. The main questions it aims to answer are:

Is letrozole plus levothyroxine superior to letrozole alone in achieving ovulation in these patients? Does combining levothyroxine with letrozole lead to higher pregnancy and live birth rates compared to letrozole alone?

Participants will be randomized into two groups:

Group 1 will receive letrozole only, starting at 2.5 mg daily from day 3 to 7 of the menstrual cycle. The dose will be increased up to 7.5 mg if no ovulation occurs, for a maximum treatment period of 6 months or until pregnancy is achieved.

Group 2 will receive letrozole at the same doses as group 1 plus 25 mcg levothyroxine daily.

Eligibility

Inclusion Criteria:

Age between 20-40 years

BMI between 18-35 kg/m2

        Meet diagnostic criteria for PCOS based on the Rotterdam consensus criteria and ESHRE/ASRM
        modifications (2018):
        Oligo- and/or anovulation Clinical and/or biochemical signs of hyperandrogenism Polycystic
        ovaries on ultrasound
        Subclinical hypothyroidism defined as TSH level between 5-10 mIU/L with normal free T4
        Infertility duration ≥ 1 year
        Intact ovaries and uterus, confirmed by physical exam and imaging
        Normal semen analysis in male partner
        No tubal or peritoneal factor contributing to infertility
        Effective contraception if not attempting conception
        Willing and able to provide informed consent
        Exclusion Criteria:
        Known thyroid disease or on thyroid medications
        Abnormal thyroid function tests other than subclinical hypothyroidism
        Hyperprolactinemia
        Presence of other causes of infertility such as:
        Moderate to severe male factor infertility Bilateral tubal occlusion or peritoneal factors
        Stage III-IV endometriosis Ovarian failure or insufficiency (high FSH or low AMH)
        Previous diagnosis of any type of congenital adrenal hyperplasia
        Uncontrolled diabetes (HbA1C >8%)
        History of deep vein thrombosis or thromboembolic events
        Any contraindication to letrozole or levothyroxine
        Previous use of letrozole or levothyroxine in past 6 months
        Current or suspected pregnancy
        Breastfeeding
        Inability to comply with treatment and follow-up procedures